Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-2 and its receptors are present in hippocampal structures, particularly the pyramidal cell layer. In the present study, we examined the interaction between recombinant human interleukin-2 (rhIL-2) and the voltage-dependent calcium (Ca2+) current using the whole-cell patch-clamp technique. RhIL-2 depressed a fraction of the inward Ca2+ current in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is rapid, dose-dependent with 0.001-1.0 ng rhIL-2/10 microliters (6.8 x 10(-12) to 6.8 x 10(-9) M) and reversible in > 80% of the neurons. Heat-inactivated rhIL-2 had no effect. The application of anti-rhIL-2 monoclonal antibody inhibited the rhIL-2-induced depression of the Ca2+ current. The depression of the Ca2+ current by IL-2 may play a role in the induction and/or progression of neuropathological processes of immunological origin, and in the induction of neurological manifestations during IL-2 immunotherapy.
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PMID:Interleukin-2 modulates calcium currents in dissociated hippocampal CA1 neurons. 839 Mar 10

The accelerated (24 h) rejection of (LEWxBN)F1 cardiac allografts (Tx) in LEW rats sensitized with BN skin grafts, is abrogated with CD4 mAb (BWH-4) administration between skin (day -7) and heart (day 0) transplantation (Tx survival ca. 11 days, p < 0.0001). This study analyzed the effects of CD4-targeted therapy upon host IgG and IgM alloantibody (allo-Ab) within the serum by two-color flow cytometry, and within the Tx, by immunohistology. These data were correlated with mRNA and protein production profiles of Th1 (IL-2, IFN-gamma) vs Th2 (IL-4) specific cytokines (polymerase chain reaction and/or immunohistology). Skin grafts elicited a strong systemic IgM allo-Ab response, which peaked at the time of cardiac Tx rejection at 24 h. It was associated with extensive deposits of IgM on Tx endothelium. Treatment with BWH-4 mAb diminished circulating IgM allo-Ab levels, and only low levels of IgM could be detected at the Tx site. Conversely, the low circulating IgG allo-Ab levels during rejection at 24 h in untreated recipients were accompanied by a strong labeling for intra-Tx IgG. BWH-4 mAb therapy did not prevent totally the switch of the IgM to IgG, but the IgG allo-Ab response was earlier, less intense and more transient than in untreated recipients. Accelerated rejection triggered sequential lymphokine mRNA expression in cardiac Tx, with the peak of transcription for IL-2 (6-12 h) preceding that for IL-4 (24 h). Interestingly, although CD4 targeted therapy virtually ablated the induction of IL-2 mRNA, it preserved transcription of the IL-4 gene. BWH-4 mAb therapy decreased otherwise abundant intra-Tx IL-2 and IFN-gamma, but allowed a vigorous elaboration of IL-4, confirming the translation of mRNA to the protein in vivo. Thus, CD4 mAb-mediated abrogation of accelerated cardiac Tx injury correlates with suppression of Th1 responses (depressed IL-2 and IFN-gamma production), but sparing of the Th2 function (enhanced IL-4 elaboration). Indeed, CD4 mAb-induced allo-Ab depression and immunosuppressive effects may reflect selective targeting of proinflammatory Th1-like cells and the multifaceted effects of IL-4 produced by unopposed Th2-like cells.
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PMID:CD4 mAb therapy modulates alloantibody production and intracardiac graft deposition in association with selective inhibition of Th1 lymphokines. 840 56

The production of the cytokines interferon gamma (IFN gamma), interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) was investigated in the mitogen-stimulated whole blood cell culture media from 51 patients with urinary bladder carcinomas, 52 patients with renal carcinomas, 31 patients with prostatic carcinomas and 360 healthy controls. The cytokines were measured 4 days after induction by a sensitive enzymo-immunological assay. In the blood cell culture supernatants of the patients with urinary bladder carcinomas significant lower levels of IFN gamma (P < or = 0.001), IL-2 (P < or = 0.01) and TNF alpha (P < or = 0.05) were found as compared to the controls. Blood cells of patients with renal carcinomas had lower production of IFN gamma (P < or = 0.01), IL-2 (P < or = 0.001) and IL-1 alpha (P < or = 0.01), whereas the values of the total group of patients with prostatic carcinomas were not significantly different from those of the controls. Lymphocyte and monocyte counts were almost identical in the control and all tumor patient groups. When the patients with renal carcinomas and prostatic carcinomas were analyzed according to their different clinical stages we could show a gradual depression of the IFN-gamma levels, which was related to tumor burden.
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PMID:Impaired cytokine production in whole blood cell cultures of patients with urological carcinomas. 849 65

SK&F 105685 is a novel azaspirane with immunosuppressive activity in animal models of autoimmune disease. This study evaluates the efficacy and mechanism of action of the compound in rat recipients of cardiac allografts. Short-term SK&F 105685 therapy (20 mg/kg/day by gavage) proved effective both in the pretreatment (days -14 to -8 or -7 to -1; allograft at day 0) and treatment (days 0 to 6) protocols, with cardiac allograft survival prolonged to 14-17 days (acute rejection = 7 days; P < 0.001). SK&F 105685 pretreatment exerted at least additive effects with subtherapeutic CsA (1.5 mg/kg/day x 7 days i.m.) given after transplantation, with 50% of allografts surviving > 50 days. SK&F 105685 therapy diminished the immunohistological features of acute rejection, with the cellular infiltrate suppressed and the induction of IL-2/transferrin receptors, and elaboration of IL-2/IFN-gamma essentially abolished, as compared with the grafts in untreated hosts. These correlated with normal frequency of CD4, CD5, CD8 phenotype subsets and B cells in recipient lymphoid organs, as shown by flow microfluorimetry. Adoptive transfer of untreated or x-irradiated (2000 rads) spleen cells from SK&F 105685-modulated hosts significantly prolonged the survival of donor-specific or third-party test cardiac allografts to 10-15 days, suggesting the presence of nonspecific x-irradiation-resistant suppressor cells in the transferred inoculum. Their activity could be enriched by Percoll density centrifugation and screened by the ability to inhibit Con A-driven proliferation of normal cells in the coculture assay. The light-density x-irradiation-resistant spleen cell fraction (1.07 g/ml) was consistently and significantly more suppressive than the heavy-density (1.09 g/ml) interface, or the corresponding unseparated cells. Thus SK&F 105685 therapy abrogates rejection response and significantly prolongs the survival of vascularized cardiac allografts in rats. This effect is associated with selective depression of host alloreactivity/immune activation at the graft site, and simultaneous induction of suppressor cells in recipient spleen, comparable to natural or nonspecific suppressor cells generated by TLI. This unique activity profile is consistent with the concept that SK&F 105685 should be considered as a critical chemical adjunct in novel therapeutic strategies representing TLI-equivalent.
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PMID:Induction of nonspecific x-irradiation-resistant suppressor cell activity in vivo and prolongation of vascularized allograft survival by SK&F 105685, a novel immunomodulatory azaspirane. 851 8

Treatment with rapamycin (RPM) prevents accelerated rejection of (LEW x BN)F1 cardiac allografts in LEW rats presensitized with BN skin grafts. This study analyzed the influence of RPM on cytokine (IL-2, IL-4, IL-10, and IL-12) and alloantibody networks in this model. Accelerated (24-h) rejection was associated with strong expression of intragraft IL-2 and IL-12 (p40) mRNAs, which reached maximal levels 3 to 6 h post-transplantation. IL-4 and IL-10 mRNAs were readily detectable throughout the observation period. RPM therapy abrogated rejection at 24 h and prolonged cardiac allograft survival to about 50 days. This effect was correlated with a profound initial depression of IL-2 mRNA; delayed expression of IL-2 mRNA was detected in well functioning grafts at > 20 days. In RPM-treated hosts, expression of IL-12 (p40) mRNA was low at the early time points (6-24 h), but prominent in long term grafts. The expression of both IL-4 and IL-10 mRNAs was preserved in RPM-conditioned hosts. Immunohistologic analysis of long term allografts revealed an interstitial cellular infiltrate and areas of intimal proliferation within small arteries indicative of early transplant arteriosclerosis. Analysis of cytokine proteins showed dense labeling of mononuclear and some endothelial cells for IL-4 and IL-12 (p70), but not for IL-2 or IFN-gamma alloantibody in the early post-transplant period. However, an increase in circulating and intragraft IgM and, to a lesser extent, IgG, primarily of the IgG2b subclass, was evident in long term recipients. Thus, RPM treatment reduces, but does not completely inhibit, the expression of Th1-type and preserves the expression of Th2-type cytokines. The demonstration of IL-12 in long term allografts after RPM therapy may reflect late activation of macrophages that, coupled with the appearance of IgG2b, may contribute to the chronic rejection of cardiac allografts.
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PMID:Cytokine and alloantibody networks in long term cardiac allografts in rat recipients treated with rapamycin. 859 90

Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This depression is associated with the presence of a circulating myocardial depressant substance with physical characteristics consistent with cytokines. The present study utilized an in vitro myocardial cell assay to examine the role of various human recombinant cytokines, including tumor necrosis factor (TNF)alpha and interleukin (IL)1beta, in depression of cardiac myocyte contractile function induced by serum from humans with septic shock. The extent and velocity of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed loop video tracking system. Individually, TNF-alpha and IL-1beta each caused significant concentration-dependent depression of maximum extent and peak velocity of myocyte shortening in vitro. In combination, TNF-alpha and IL-1beta induced depression of myocardial cell contractility at substantially lower concentrations consistent with a synergistic effect. Using immunoabsorption, removal of both TNF-alpha and IL-1beta (but not either alone) from the serum of five patients with acute septic shock and marked reversible myocardial depression resulted in elimination of serum myocardial depressant activity. IL-2, -4, -6, -8, -10, and interferon gamma failed to cause significant cardiac myocyte depression over a wide range of concentrations. These data demonstrate that TNF-alpha and IL-1beta cause depression of myocardial cell contraction in vitro and suggest that these two cytokines act synergistically to cause sepsis-associated myocardial depression in humans.
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PMID:Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. 864 98

The thymoma cell line EL4.IL-2 (EL-4) was used as a T-cell model to assess the immunotoxic effects of several mycotoxins produced by the Aspergillus-Penicillium and the Fusarium groups. EL-4 cells were stimulated with phorbol 12-myristate 12-acetate (PMA) in the presence of mycotoxins at various concentrations for 5 d and culture supernatants were analyzed for interleukins (IL) IL-2 and IL-5 by enzyme-linked immunosorbent assay (ELISA). The cytokine effects were further related to proliferation and cell viability using the MTT [3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay with absorbance at 570 nm (A570) as the endpoint indicator. IL-2 and IL-5 levels were dramatically increased by cyclopiazonic acid at 50-1000 ng/ml, whereas IL-2 was significantly decreased at 10 microgram/ml. Proliferation was slightly increased at 100-1000 ng/ml cyclopiazonic acid but markedly depressed at 5 and 10 microgram/ml. When EL-4 cells were exposed to 5 and 10 microgram/ml of ochratoxin A, IL-2 production was markedly increased while IL-5 production was significantly decreased. The A570 was significantly decreased by ochratoxin A at 10 microgram/ml. IL-2 and Il-5 production was almost totally suppressed by patulin at concentrations > or = 500 ng/ml and by T-2 toxin at > or = 5 ng/ml. These effects occurred concurrently with marked depression of A570 in the MTT assay. Although A570 was unaffected by either zearalenone or alpha-zearalenol exposure, both IL-2 and IL-5 levels were significantly elevated by these toxins at 5 or 10 microgram/ml. IL-2 and IL-5 production were not affected in EL-4 cells cultured with either the Aspergillus-Penicillium toxins aflatoxin B1 and secalonic acid or the Fusarium toxins wortmannin, fumonisin B1, or fusaric acid at concentrations up to 10 microgram/ml. In total, the EL-4 culture studies indicated that cyclopiazonic acid, ochratoxin A, zearalenone, and alpha-zearalenol could stimulate cytokine production whereas patulin and T-2 toxin were inhibitory. Cytokine dysregulation was not always related directly to perturbations in proliferation. The results suggest that the EL-4 thymoma cell line could be a simple and effective in vitro model for evaluating immunotoxicity of various classes of environmental chemicals.
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PMID:Effects of mycotoxins on cytokine production and proliferation in EL-4 thymoma cells. 869 8

There is accumulating evidence that inflammatory cytokines are involved in the pathophysiology of cardiac dysfunction found in sepsis, myocardial infarction and acute rejection after heart transplantation. Although there are some previous reports on cytokines and myocardial depression, myocardial energy metabolism caused by cytokines have not been established yet. The purpose of the present study is to determine if the IL-2 effect on contractile function is related to impaired energy production. In isolated perfused rabbit hearts (n = 6), we measured developed pressure, ATP and phosphocreatine by 31P-NMR spectroscopy during and after a 5 minute infusion of IL-2 (200 U/ml/min). Although there was slightly increased inorganic phosphate which might be affect on myocardial contractility reduced, high energy phosphate and intracellular pH did not change by IL-2 infusion, suggesting another mechanism for myocardial depression caused by inflammatory cytokine, IL-2.
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PMID:[Cardiac disfunction and myocardial energy metabolism caused by interleukin-2 (IL-2)]. 872 57

The macrophage theory of depression proposes that abnormal secretions of the macrophage cytokines, an increase in interleukin (IL) 1, and a decrease in IL-2 may cause depression. The olfactory bulbectomized (OB) rat has been developed as an animal model of depression. In the present study, the effects of intracerebroventricular administration of IL-2 (10 U) for 7 days on behaviour, neurotransmitter concentrations, corticosterone levels, and some immune functions were investigated. In the novel environment of the 'open-field' apparatus, the OB rat showed increases in ambulation, rearing, grooming, and defaecation scores as compared with sham-operated animals. Following IL-2 administration, grooming and defaecation were significantly attenuated, while the ambulation and rearing scores were unaffected. In the elevated plus-maze, the increase in the time spent on the open arms of the maze by the OB animal was normalized by IL-2 administration. In the brain of untreated OB rats, the concentrations of noradrenaline were reduced; IL-2 treatment significantly increased the concentrations of noradrenaline and serotonin. After administration of IL-2 for 7 days, the impairments in the immune functions were also largely reversed in OB rats. Thus IL-2 significantly normalized the hyperactivity of mononuclear cells, the suppression of lymphocyte proliferation, and the reduction in the monocyte percentage in the white blood cell count in the OB rat. The concentrations of corticosterone in the serum of the OB rat were significantly reduced, but returned to control values following IL-2 treatment. The results suggest that IL-2 may have modulatory functions on behavioural, neurochemical, hormonal, and immunological aspects of the OB rat model of depression.
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PMID:Interleukin-2-induced changes in behavioural, neurotransmitter, and immunological parameters in the olfactory bulbectomized rat. 873 99

Cytokine production was previously demonstrated to be reduced in untreated major affective patients. In addition, recovery from depression following clomipramine (CMI) treatment was accompanied by the restoration of interleukin-1 beta (IL-1 beta) and interleukin-3-like activity (IL-3-LA) to normal range. In the present study we assessed the in vitro production of IL-1 beta IL-2, and IL-3-LA by peripheral blood mononuclear cells (PBMC) in 11 nondepressed patients with obsessive compulsive disorder (OCD) before and after 8 weeks of CMI treatment. Results were compared with those of 11 healthy subjects. CMI treatment induced a significant improvement in OCD symptoms. No alteration was observed in cytokine production in OCD patients before treatment as compared to control subjects. Moreover, 8 weeks of drug treatment had no effect on cytokine production. In conclusion, OCD per se, as well as CMI treatment, have no effect on interleukin production as measured in this study.
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PMID:Cytokine production in obsessive-compulsive disorder. 942 92


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